The First Reported Halogenation of a tert-Butyl Group with HCl or HBr in CHCl3. Unexpected Differences in the Reactions of HCl, HBr, HI, and HF with sp-9-(o-ferf-Butylphenyl)-9-fluorenol

Article abstract of DOI:10.1021/jo9910280

The reactions of sp-9-(o-tert-butylphenyl)-9-fluorenol (1) with HCl, HBr, HI, and HF, respectively, were found to follow diverse pathways. Most unexpected is the unprecedented monohalogenation of a tert-butyl group, sp-9-[o-(β-chloro-α,α-dimethylethyl)phenyl]fluorene (2) being formed quantitatively from 1 treated with HCl-CHCl₃ and sp-9-[o-(β-bromo-α,α-dimethylethyl)phenyl]fluorene (3) (>90%), along with a very small amount of sp-9-(o-tert-butylphenyl)fluorene (4), being formed from 1 treated with HBr-CHCl₃. The absolute structure of 2 was ascertained by X-ray crystal analysis. Likewise, the expected 9-chloro- and 9-bromofluorenes from the usual substitution of OH by halogen in reactions of alcohols with SOCl₂ and SOBr₂ were not obtained from treatment of 1 with these reagents; the only products were 2 and 3, respectively. These products are formed by nucleophilic attack of halide ion on a tert-butyl methyl group of the 9-cation (1a) with concerted intramolecular displacement of hydride to 9-C⁺, while 4 results from the slower electron transfer from Br to 1a to form free radical 1b, which captures an H atom from HBr. The high redox potential of I^- and weak HI bond ensures the rapid conversions 1a → 1b → 4, making 4 the exclusive product from treatment of 1 with HI-CHCl₃. In contrast to the other halides, fluoride is a poor nucleophile in displacement reactions and poor electron-transfer agent. Consequently, strongly electrophilic 1a reacts with F^- to provide sp-9-(o-tert-butylphenyl)-9-fluorofluorene (5) as the only product from the reaction of 1 with pyridine (HF)_x. Dynamic NMR provided strong evidence that the reaction with HI occurs with inversion, the ap rotamer (4a) of 9-(o-tert-butylphenyl)fluorene being formed initially, followed by rotation to the isolated sp rotamer, 4. The largely planar configuration of C-9 of the unsymmetrically hindered cation intermediate 1a, responsible for this inversion and the related inversions, was supported by NMR.

Full text of DOI:10.1021/jo9910280

9444
J . Org. Chem. 1999, 64, 9444-9449
Th e F ir st Rep or ted Ha logen a tion of a ter t-Bu tyl Gr ou p w ith HCl
or HBr in CHCl3. Un exp ected Differ en ces in th e Rea ction s of HCl,
HBr , HI, a n d HF w ith sp-9-(o-ter t-Bu tylp h en yl)-9-flu or en ol
Cal Y. Meyers,* Yuqing Hou, Hisham G. Lutfi,† and Howard L. Saft‡
Department of Chemistry and Biochemistry, Southern Illinois University, Mail Code 4409,
Carbondale, Illinois 62901
Received J une 28, 1999
The reactions of sp-9-(o-tert-butylphenyl)-9-fluorenol (1) with HCl, HBr, HI, and HF, respectively,
were found to follow diverse pathways. Most unexpected is the unprecedented monohalogenation
of a tert-butyl group, sp-9-[o-(â-chloro-R,R-dimethylethyl)phenyl]fluorene (2) being formed quanti-
tatively from 1 treated with HCl-CHCl3 and sp-9-[o-(â-bromo-R,R-dimethylethyl)phenyl]fluorene
(3) (>90%), along with a very small amount of sp-9-(o-tert-butylphenyl)fluorene (4), being formed
from 1 treated with HBr-CHCl3. The absolute structure of 2 was ascertained by X-ray crystal
analysis. Likewise, the expected 9-chloro- and 9-bromofluorenes from the usual substitution of OH
by halogen in reactions of alcohols with SOCl2 and SOBr2 were not obtained from treatment of 1
with these reagents; the only products were 2 and 3, respectively. These products are formed by
nucleophilic attack of halide ion on a tert-butyl methyl group of the 9-cation (1a ) with concerted
intramolecular displacement of hydride to 9-C+, while 4 results from the slower electron transfer
from Br- to 1a to form free radical 1b, which captures an H atom from HBr. The high redox potential
of I- and weak HI bond ensures the rapid conversions 1a f 1b f 4, making 4 the exclusive product
from treatment of 1 with HI-CHCl3. In contrast to the other halides, fluoride is a poor nucleophile
in displacement reactions and poor electron-transfer agent. Consequently, strongly electrophilic
1a reacts with F- to provide sp-9-(o-tert-butylphenyl)-9-fluorofluorene (5) as the only product from
the reaction of 1 with pyridine.(HF)x. Dynamic NMR provided strong evidence that the reaction
with HI occurs with inversion, the ap rotamer (4a ) of 9-(o-tert-butylphenyl)fluorene being formed
initially, followed by rotation to the isolated sp rotamer, 4. The largely planar configuration of C-9
of the unsymmetrically hindered cation intermediate 1a , responsible for this inversion and the
related inversions, was supported by NMR.
In tr od u ction
prepare 9-chloro- and 9-bromo-9-(o-tert-butylphenyl)-
fluorene to determine the relative stabilities of their
respective ap (2a , 3a ) vs sp (2b, 3b) rotamer configura-
tions and corresponding reactivities.9,10 We explored the
possibility of utilizing hydrogen halides to convert sp-9-
(o-tert-butylphenyl)-9-fluorenol (1) into the desired prod-
ucts. Halides differ from each other significantly in
nucleophilicity, size, and redox potential. In our study
of the reactions of 1 with HCl, HBr, HI, and pyridine‚
(HF)x, respectively, these different properties came into
play and led to entirely different types of products. Of
special note is the unexpected and unprecedented mono-
halogenation of a tert-butyl group with a hydrogen halide.
Treatment of 1 with HCl-CHCl3 quantitatively provided
sp-9-[o-(â-chloro-R,R-dimethylethyl)phenyl]fluorene (2),
and treatment with HBr-CHCl3 afforded >90% of sp-9-
[o-(â-bromo-R,R-dimethylethyl)phenyl]fluorene (3). In nei-
In our studies of rotationally restricted, sterically
hindered 9-substituted fluorenes,1-8 we attempted to
* To whom correspondence should be addressed. E-mail: cal@
chem.siu.edu. Fax: 618-453-6408.
† Present address: Department of Chemistry, University of Toronto,
Toronto, ON, Canada M5S 3H6.
‡ Summer Undergraduate Chemistry Research Participant at South-
ern Illinois University, Carbondale, 1995; from the University of
Florida, Gainesville.
(1) A major part of this work was carried out by Hou, Y. Ph.D.
Dissertation, Southern Illinois University, Carbondale, IL, 1997.
(2) (a) Meyers, C. Y.; Chan-Yu-King, R.; Wahner, A. P.; Manohar,
S. K.; Carr, S. E.; Robinson, P. D. Acta Crystallogr. 1991, C47, 1236-
1239. (b) Meyers, C. Y.; Tunnell, J . L.; Robinson, P. D.; Hua, D. H.;
Saha, S. Acta Crystallogr. 1992, C48, 1815-18. (c) Robinson, P. D.;
Lutfi, H. G.; Lim, L. W.; Meyers, C. Y. Acta Crystallogr. 1994, C50,
1728-1732. (d) Meyers, C. Y.; Hou, Y.; Scott, D.; Robinson, P. D. Acta
Crystallogr. 1997, C53, 1149-1151. (e) Hou, Y.; Meyers, C. Y.;
Robinson, P. D. Acta Crystallogr. 1998, C54, 1013-1016.
(3) Robinson, P. D.; Hou, Y.; Meyers, C. Y. Acta Crystallogr. 1998,
C54, 1173-1175.
(4) Meyers, C. Y.; Hou, Y.; Lutfi, H. G.; Robinson, P. D. National
Meeting of the American Chemical Society, Chicago, Aug 20-24, 1995;
Abstract No. ORGN 297.
(5) Meyers, C. Y.; Hou, Y.; Lutfi, H. G.; Robinson, P. D.; Dunn, H.
E.; Seyler, J . W. National Meeting of the American Chemical Society,
San Francisco, Apr 13-17, 1997, Abstracts ORGN 351.
(6) Meyers, C. Y.; Hou, Y.; Robinson, P. D. Acta Crystallogr. 1999,
C55, 626-628.
(9) The designations sp (synperiplanar) and ap (antiperiplanar) for
these fluorene rotamers are in accord with Rule E-6.6, IUPAC
Tentative Rules, Section E, Fundamental Stereochemistry (J . Org.
Chem. 1970, 35, 2861).
(10) The ap and sp stereochemistry of a number of 9-(o-tert-
butylphenyl)fluorenes in the crystalline state has been unequivocally
determined by X-ray diffraction. In solution, they are effectively
characterized by 1H NMR spectroscopy. The most striking differences
emanate from the o-tert-butyl protons. In the ap rotomers these protons
are shielded by the fluorene π electrons and resonate upfield in the
0.7 ppm region, while in the sp rotomers they are correspondingly
deshielded and resonate downfield in the 1.8 ppm region. Differences
are also observed in the resonances of the ortho-H of ap vs sp rotamers
and of the H-9 of these rotamers of 9-(o-tert-butylphenyl)fluorene itself.
See refs 1, 2d,e, 3, 6-8, and 11.
(7) (a) Robinson, P. D.; Hou, Y.; Meyers, C. Y. Acta Crystallogr. 1998,
C54, CIF Access paper, DVN IUC9800051. (b) Hou, Y.; Meyers, C. Y.
Can. J . Chem, 1999, 77, 960-966.
(8) Robinson, P. D.; Hou, Y.; Lutfi, H. G.; Meyers, C. Y. Acta
Crystallogr. 1998, C54, 73-77.
10.1021/jo9910280 CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/01/1999

Halogenation of a tert-Butyl Group with HCl or HBr
J . Org. Chem., Vol. 64, No. 26, 1999 9445
Sch em e 2
F igu r e 1. ORTEP of 2.
Sch em e 1
Sch em e 3
ther case was the desired 9-halo product isolated, al-
though its fleeting presence was observable in some
instances when the reaction was carried out in an NMR
tube and monitored. The structure of 2 was unequivocally
confirmed by X-ray crystal analysis (Figure 1).3 Reaction
of 1 with HI-CHCl3 failed to produce any halogenated
product; sp-9-(o-tert-butylphenyl)fluorene (4) was formed
exclusively. Finally, of the hydrogen halides, only HF
provided the expected 9-halo product, sp-9-(o-tert-butyl-
phenyl)-9-fluorofluorene (5) being the exclusive product
from the reaction of 1 with pyridine.(HF)x. These trans-
formations are summarized in Scheme 1.
nism leading to the halogenation of the tert-butyl group
of 1 treated with HCl, HBr, SOCl2, or SOBr2, respectively,
is illustrated in Scheme 2. Small yields of 2 were observed
in reactions of 1 with [ClC(O)]2, CH3C(O)Cl, and (CF3-
SO2)2O/n-Bu4N+Cl-, respectively, and 3 was a product
obtained in the reaction 1 or its lithiated salt with
(CF3SO2)2O/n-Bu4N+Br-. Treatment of sp-9-(o-tert-butyl-
phenyl)-9-fluorenyl methyl ether (6b) with HBr-CHCl3
also provided 3 almost exclusively (Scheme 3). A related
study showed that 9-deuterated 4, neutral or acidified
with triflic acid, was passed through a silica gel column
without undergoing any D/H exchange. These results and
the fact that products 2 and 3 possessed 9-H regardless
of whether the substrate was 1 or 1-OD, the reagent was
the corresponding hydrogen halide or the other reactive
halogen compounds, or the solvent was CHCl3, CDCl3,
or CH2Cl2, prove that the 9-H atom in these products
emanated from the (tert-butylphenyl)fluorene moiety
itself and most probably from the tert-butyl group.
Chlorination and bromination of a tert-butyl group with
the respective hydrogen halide or thionyl halide appar-
Resu lts a n d Discu ssion
Ha logen a tion of th e ter t-Bu tyl Gr ou p . The desired
9-chloro- and 9-bromofluorenes from the usual substitu-
tion of OH by halogen in reactions of alcohols with SOCl2
and SOBr2 also were not obtained from the treatment of
1 with these reagents. Instead, only monohalogenation
of the tert-butyl group occurred, with 2 and 3, respec-
tively, being formed as the major products. The mecha-

9446 J . Org. Chem., Vol. 64, No. 26, 1999
Meyers et al.
Sch em e 4
Sch em e 5
step, 9-OH f 9-OCH3, via cation 1a , which is attacked
on its less hindered face by CH3OH.1 A parallel inversion
via free radical 1b was indicated by a dynamic NMR
study (vide infra). The stereochemical consequences of
the reactions described here were confirmed in our
studies employing chiral substrates1 and will be reported
subsequently.
ently have not previously been reported. In the case of
these halogenations occurring with 1, special circum-
stances prevail. As illustrated in Scheme 2, initial
formation of the expected relatively stable fluorenyl
cation 1a is followed by halide attack on C-9+, directly
producing ap-9-(o-tert-butylphenyl)-9-chlorofluorene (2a )
and ap-9-(o-tert-butylphenyl)-9-bromofluorene (3a ), re-
spectively. Because of the strain imposed on the ap
rotamers of 9-(o-tert-butylphenyl)fluorenes by the tert-
butyl group impinging on the fluorene ring’s π electrons,
rotation to the thermodynamically preferred sp rotamers
generally occurs.2d,e,4-7,11,12 However, like the correspond-
ing ap rotamers of 9-(o-tert-butylphenyl)-9-methylfluo-
rene (7) and 9-(o-tert-butylphenyl)-9-methylthiofluorene
(8),6,7 the ap rotamers 2a and 3a are the preferred
configurations because the steric interaction between the
large 9-substituent and the tert-butyl group in the sp
rotamers (2b, 3b) effects an even greater strain. While
7 is strained, it is stable, but 8 undergoes homolysis of
the S-fluorenyl bond on standing to provide CH3S. and
fluorenyl radical 1b, which leads to the formation of sp-4
and sp-9-(o-tert-butylphenyl)-3-methylthiofluorene (9)
(Scheme 4).7 Likewise, 2a and 3a undergo halogen C-9
cleavage, but heterolytically and more rapidly than 8, and
cannot be isolated. The equilibria 2a h 1a and 3a h 1a
allow the halide ions to attack a tert-butyl methyl group
whose hydride simultaneously is transferred to the
cationic C-9. This is, in essence, an SN2 reaction in which
the leaving group is a hydride attracted to a cation by
their intramolecular proximity, leading to thermody-
namically favored bond formation. In support of this
mechanism is our observation that cation 1a , in the
absence of halide ions, has a longevity of at least several
days, and its NMR spectra were recorded (vide infra).
This type of SN2 displacement of hydride is unusual and
should not be deemed similar to the common intramo-
lecular hydride shift leading to a more stable carbocation.
As illustrated in Scheme 2, the conversion of 1 to 2
and 3, respectively, via this mechanism would afford
configurational retention.1 Likewise, as shown in Scheme
3, similar treatment of the 9-methoxy derivative 6b with
HBr-CHCl3 also provided 3 and, presumably, with
retention of configuration. However, this scheme also
illustrates that the sequential conversion 1 f 6a f 6b
f 3 (or 2) involves inversion, which occurs in the initial
Rep la cem en t of th e 9-OH by H. The ability of halide
ions to donate an electron increases in the order F-
<
Cl- < Br- < I-, the respective standard reduction
potentials of the corresponding halogens being 2.87,
1.3583, 1.065, and 0.5338 V.13 The reduction potential of
fluorenyl cation has been reported to be 0.76,14 0.68,15
and 0.8516 V. In light of the sterically imposed instability
of the 9-Cl and 9-Br ap compounds 2a and 3a , the further
enhanced steric strain enforced by the even larger iodine
atom would almost certainly preclude the formation of
the corresponding 9-I compound, if not the transition
state required for the attack by I- on cation 1a . The
combination of redox potentials of I- and fluorenyl cation
apparently favors exclusive electron transfer in the
reaction of 1 with HI-CHCl3 over nucleophilic hydride
displacement of the type followed by Cl- and Br-. As
illustrated in Scheme 5, single electron transfer from HI
to initially formed cation 1a provides free radical 1b,
which, in turn, abstracts a hydrogen atom from HI to
form ap-(o-tert-butylphenyl)fluorene (4a ). Rapid rotation
of 4a provides the thermodynamically preferred sp rota-
mer, 4, the quantitatively isolated product.
The stereochemistry of this transformation was sug-
gested when the reaction was carried out at -50 °C and
continuously monitored by dynamic NMR. At -40 °C, the
exclusive formation of ap rotamer 4a was observed, as
reflected by the sharp singlet at δ 0.69 representing the
highly shielded tert-butyl group. Rotation to sp 4 occurred
as the temperature was allowed to rise; the singlet at δ
1.72 of its deshielded tert-butyl group appeared and grew
in intensity as that at δ 0.69 was correspondingly
reduced. Rotomerization was essentially complete at 20
(11) Oh ki, M. In The Chemistry of Rotational Isomers; Hafner, K.,
Lehn, J .-M., Rees, C. W., Schleyer, P. v. R., Trost, B. M., Zahradn´ık,
R., Eds.; Springer-Verlag: New York, 1993; Reactivity and Structure
Concepts in Organic Chemistry, Vol. 30, and references therein.
(12) Nakamura, M.; Nakamura, N.; Oh ki, M. Bull. Chem. Soc. J pn
1977, 50, 2986-2990.
(13) Hunsberger, J . F. In Handbook of Chemistry and Physics, 50th
ed.; Weast, R. C., Ed.; Chemical Rubber Publishing Co.: Cleveland,
OH, 1970; p D-109.
(14) Wayner, D. D. M.; McPhee, D. J .; Griller, D. J . Am. Chem. Soc.
1988, 110, 132-137.
(15) Bordwell, F. G.; Bausch, M. J . J . Am. Chem. Soc. 1986, 108,
1979-1985.
(16) Lockert, P.; Federlin, P. Tetrahedron Lett. 1973, 1109-1112.

Halogenation of a tert-Butyl Group with HCl or HBr
J . Org. Chem., Vol. 64, No. 26, 1999 9447
Sch em e 6
Sch em e 7
°C. These results suggested that the conversion of 1 to
4a proceeds via initial inversion followed by rotation, a
mechanism that was strongly supported by related
reactions carried out with chiral substrates.1 This SET
mechanism and the fact that the redox potential of Br-
is between that of I- and Cl- account for our observations
that the reactions of 1 or 6b with HBr always provided
a small amount of 4 along with 3, while the reactions of
1 with HCl, SOCl2, oxalyl chloride, or acetyl chloride
produced 2 but no 4. It should be pointed out that
reactions of 1 with triflic anhydride/n-Bu4N+Cl- or Br-
always provided substantial amounts of 4 along with
small amounts of 2 or 3, but the formation of 4 resulted
from a mechanism entirely different from that described
above.1,7b
Rep la cem en t of 9-OH by F . Of the four halide ions,
F- is the smallest, least nucleophilic in displacement
reactions and has the poorest electron-transfer ability.
Ironically, because of these characteristics, the required
intermediacy of cation 1a , and the specific steric require-
ments imposed by the hindered 9-(o-tert-butylphenyl)-
fluorenyl system, only F- provides the “expected” 9-halo
product. Scheme 6 illustrates the conversion of 1 with
pyridine‚(HF)x to cation 1a , which provides ap-9-(o-tert-
butylphenyl)-9-fluorofluorene (5a ) by attack of F- at C-9.
As described for the other reactions, attack on cation 1a
most reasonably occurs on the less hindered face, giving
rise to inversion at C-9. Rapid rotation leads to the almost
quantitative isolation of the thermodynamically preferred
sp rotamer 5.
NMR Id en tifica tion of 9-(o-ter t-Bu tylp h en yl)-9-
flu or en yl Ca tion (1a ). As a means to support the
suggested sp2 hybridization of C-9 of cation 1a and,
therefore, the stereochemistry of its o-tert-butylphenyl
moiety as being between that of the ap and sp rotamers,
9-(o-tert-butylphenyl)-9-fluorenyl triflate (10) was pre-
pared. The blood-red solution in CDCl3 indicated that 10
in this medium exists as its dissociated salt, so that an
NMR spectrum would be that of cation 1a . The observed
singlet at δ 1.51 was ascertained to be associated with
the tert-butyl hydrogens on the basis of its integration
relative to that of the aromatic protons. The correct ratio,
9:12, was observed, indicating the exclusivity of salt 10
relative to the ap and sp esters, 10a and 10b. The
resonance in the 13C spectrum at δ 215.66 correctly
identified the 9-C+. The tert-butyl singlet at δ 1.51 of
cation 1a is indeed between that of the shielded tert-butyl
(δ 0.69) of ap 4a and deshielded tert-butyl (δ 1.72) of 4.
In contrast to the triflate, the acetate was shown to exist
exclusively as the colorless ester, 11, which showed no
indication of dissociating into the corresponding salt. The
formation and comparison of these structures are il-
lustrated in Scheme 7.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are corrected unless
1
stated otherwise. H and 13C NMR spectra were taken at 300
and 75 MHz, respectively, in CDCl3 solution, and IR spectra
were taken on Nujol mulls. Note: Trifluoromethanesulfonic
acid (triflic acid) and its anhydride are very corrosive and
hygroscopic and should be handled with extreme care.
sp-9-(o-ter t-Bu tylp h en yl)-9-flu or en ol (1) was prepared
as reported with its X-ray structure.8 The synthesis was
essentially the same as that reported earlier by the Oh ki
group.12
For m ation of sp-9-[o-(â-Ch lor o-r,r-dim eth yleth yl)ph en -
yl]flu or en e (2). Met h od A. R ea ct ion of 1 w it h HCl in
CDCl3. HCl gas, generated by the dropwise addition of concd
H2SO4 onto solid NaCl, was bubbled into CDCl3 for 30 min to
provide a saturated solution. This solution (0.5 mL) was added
to an NMR tube containing 1 (8.4 mg, 0.027 mmol). Shaking
the tube provided a colorless solution that slowly became pale
yellow within 10 min. After 45 min, NMR indicated that some
starting material (δ 1.8, singlet) was still present. Most of the
tert-butyl resonance was at δ 0.8 (broad singlet) and there was
a broad singlet at δ 1.34, a singlet at δ 8.20 and a very broad
hump at δ 8.68. After 5 h formation of 2 was detected by NMR,
although the spectrum was largely similar to the earlier ones.
After 72 h, the solution contained 26% of 2 and 41% of 1. While
the peaks at δ 1.34 and 8.20 had disappeared, the others
observed earlier were present. After 5 days the solvent was
evaporated. NMR of the residue showed it to be essentially
pure 2 (>95% yield), whose structure was verified by X-ray
diffraction3 (colorless crystals from hexanes, mp 176.5-178 °C).
1H NMR: δ 1.81 (s, 6 H), 4.16 (s, 2 H), 5.65 (s, 1 H), 6.25 (dd,
J ) 7.8, 1.5 Hz, 1 H), 6.93 (ddd, J ) 7.8, 7.2, 1.2 Hz, 1 H), 7.15
(ddd, J ) 8.1, 7.2, 1.5 Hz, 1 H), 7.25 (m, J ) 7.8, 1.2, 0.9 Hz,
4 H); 7.39 (m, J ) 7.8 Hz, 2 H); 7.45 (dd, J ) 8.1, 1.2 Hz, 1 H);
7.83 (d, J ) 7.8 Hz, 2 H). The resonance at δ 5.65 for 1 H
showed that no deuterium had been incorporated at C-9. 13C
NMR: δ 26.67, 40.98, 51.08, 55.76, 119.93, 125.09, 126.47,
127.26, 127.30, 127.44, 127,57, 131.18, 139.88, 141.02, 143.20,
149.48. IR: 3061 (w), 2953 (s), 1486 (m), 764 (m), 743 (s), 724
(m) cm-1
.

9448 J . Org. Chem., Vol. 64, No. 26, 1999
Meyers et al.
Meth od B. Rea ction of sp-9-(o-ter t-Bu tylp h en yl)flu o-
r en e-9-OD (1-OD) w ith Th ion yl Ch lor id e. To an NMR tube
containing a colorless solution of 1 (15.3 mg, 0.049 mmol) in
CDCl3 (0.6 mL) was added four drops of D2O, and the tube
was shaken and then left standing for 30 min. The D2O (top
phase) was removed via syringe, leaving a colorless solution
whose NMR spectrum exhibited no OH signal and identified
the product as 1-(9-OD). The molar ratio of residual HOD (δ
4.79) to 1-(9-OD) was 1:14.6. Thionyl chloride (14 drops) was
added, and the tube was shaken vigorously. Within 10 min
the mixture became blood red. After a few more minutes an
NMR spectrum detected the formation of 2 and also exhibited
large humps at δ 0.85 and 7.3. The deep red coloration changed
to yellow after 90 min; NMR indicated the almost-exclusive
presence of 2. No deuterium was indicated on C-9 or any other
position, and the ratio 1:2:6:1 of 9-H/ClCH2/CH3/H6′ was
identical to that of 2 obtained from the same treatment of 1
with SOCl2, which indicates that the 9-H is not derived from
the 9-OH. Purification by column chromatography and recrys-
tallization from hexanes provided white crystals having the
same mp and NMR spectra noted above for 2.
1.84 (s, 6 H), 4.09 (s, 2 H), 5.64 (s, 1 H), 6.25 (dd, J ) 1.5, 7.8
Hz, 1 H), 6.93 (ddd, J ) 1.5, 7.2 Hz, 1 H), 7.15 (ddd, J ) 1.5,
7.2, 8.1 Hz, 1 H), 7. 25 (m, J ) 1.2, 1.8, 7.5, 7.8 Hz, 4 H), 7.39
(ddd, J ) 2.1, 7.5, 7.8 Hz, 2 H), 7.47 (dd, J ) 1.2, 8.1 Hz, 1 H),
7.83 (dd, J ) 0.9, 7.5 Hz, 2 H).
13C NMR: δ 29.53, 40.30, 46.26,
51.11, 119.94, 125.17, 126.46, 127.28, 127.37, 127.57, 131.23,
139.90, 141.03, 143.26, 149.46. IR: 3061 (w), 2953 (s), 1486
(m), 764 (m), 743 (s), 724 (m) cm-1. Anal. Calcd for C23H21Br:
C, 73.21; H, 5.61. Found: C, 72.92; H, 5.74.
Meth od B. Rea ction of 1 w ith Th ion yl Br om id e. Thio-
nyl bromide (0.02 mL, 0.26 mmol) was added to a colorless
solution of 1 (28.4 mg, 0.09 mmol) in CDCl3 (ca. 0.5 mL) in an
NMR tube. After the red thionyl bromide was added, the
mixture turned yellow very rapidly. An NMR spectrum
obtained after 13 min exhibited, among other resonances, three
singlets at δ 1.84, 4.09, and 5.64 with an integration ratio of
6:2:1, indicating the initial formation of 3. The mixture was
allowed to stand for 6 days. The solvent was removed in vacuo,
and the solid residue was washed with cold hexanes. Recrys-
tallization from hexanes provided white crystalline 3, mp 186-
187.5 °C.
Meth od C. Rea ction of 1 w ith Oxa lyl Ch lor id e. Oxalyl
chloride (six drops) was added to an NMR tube containing a
colorless solution of 1 (17.1 mg, 0.054 mmol) in ca. 0.7 mL of
CDCl3. The solution became yellow on being shaken. After 30
min, its NMR spectrum indicated the presence mainly of
starting material, which was entirely consumed after 150 min.
NMR indicated that 16% of 1 was converted into 2.
Meth od D. Rea ction of 1 w ith Acetyl Ch lor id e. Acetyl
chloride (1 drop, freshly distilled, bp: 51-52 °C) was added
to an NMR tube containing a solution of 1 (19.9 mg, 0.063
mmol) in ca. 0.5 mL of CDCl3. The colorless solution was
unchanged on vigorous shaking. After 10 min, NMR exhibited
the presence of 1 and acetyl chloride in a ratio of 1:0.86. A
small additional amount of acetyl chloride was then added,
and after 90 min NMR indicated the ratio was 1:1.84. After
several days, the presence of 1 (22%), 2 (19%), and sp-9-(o-
tert-butylphenyl)-9-fluorenyl acetate (ester) (11) (vide infra)
was indicated by NMR.
Meth od C. Rea ction of 1 w ith (CF 3SO2)2O F ollow ed by
n -Bu 4N+Br _. A 10-mL one-necked, round-bottomed flask
containing a stirred colorless solution of 1 (51.9 mg, 0.17 mmol)
in 2 mL of dry CH2Cl2 was cooled in a liquid nitrogen-acetone
bath (-30 °C). Triflic anhydride (0.10 mL, 0.59 mmol) was
injected, and the solution turned deep-red immediately, indi-
cating the formation of cation 1a (triflate salt 10, vide infra).
Stirring was continued at -30 °C for 15 min; a red solid
precipitated. The liquid was removed with a pipet and a
solution of n-Bu4N+Br- (246 mg, 0.76 mmol) in 3 mL of dry
CH2Cl2 was added to the residual red solid. The cold bath was
removed, and the mixture was stirred at room temperature
for 15 min, during which time the mixture gradually became
reddish-brown. The solvent was removed in vacuo and the
residue extracted with hexanes. Evaporation of the extract in
vacuo left a brown solid that was shown by 1H NMR to contain
3 and 4 in a ratio of 3.4:1.
Meth od D. Rea ction of 1-OLi w ith (CF 3SO2)2O F ol-
low ed by n -Bu 4N+Br -. A 10-mL single-necked, round-bot-
tomed flask equipped with a stir bar and containing 1 (51.9
mg, 0.17 mmol) was sealed with a rubber septum and flushed
with argon, and 2 mL of dry ether was added. The stirred
colorless solution was cooled to -30 °C in a liquid nitrogen-
acetone bath, and an n-BuLi-hexanes solution (0.15 mL, 1.2
M, 0.18 mmol) was injected. After this colorless reaction
mixture was stirred for 10 min, triflic anhydride (0.10 mL, 0.59
mmol) was added by injection. The reaction mixture turned
deep-red immediately, indicating the formation of cation 1a
(triflate salt 10, vide infra). Stirring at -30 °C was continued
for 30 min, and the reaction setup was transferred to a drybox.
The liquid portion of the reaction mixture was removed via a
syringe and a solution of n-Bu4N+Br- (150 mg, 0.46 mmol) in
dry CH2Cl2 (3 mL) was added to the residue by injection. The
mixture became brownish yellow immediately and, after being
swirled at room temperature for 15 min, was transferred to a
separatory funnel. The reaction flask was washed with 40 mL
of ether, and the washings were transferred to the funnel. This
solution was washed with aqueous NaHCO3 and then water,
and the organic layer was dried over anhyd MgSO4, filtered,
and passed through silica gel. The solution was concentrated
in vacuo leaving a light brown solid, 55 mg, whose 1H NMR
spectrum exhibited 3 and 4 as major products in a ratio of
23:77.
Meth od E. Rea ction of 1 w ith (CF 3SO2)2O F ollow ed by
n -Bu 4N+Cl-. A 10-mL single-necked, round-bottomed flask
equipped with a stir bar and containing a colorless solution of
1 (0.171 g, 0.51 mmol) in 3 mL of CH2Cl2 was sealed with a
rubber septum and flushed with argon. The flask was im-
mersed in a liquid nitrogen-acetone bath and kept at -30 °C,
and 0.10 mL of triflic anhydride (0.59 mmol) was injected. The
mixture turned deep red immediately, indicating the formation
of cation 1a (triflate salt 10, vide infra), and was stirred at
-30 °C for 30 min, at the end of which time a solution of (n-
Bu)4N+Cl- in 3 mL of CH2Cl2 was added. The bath was
removed, and the reaction mixture was stirred at room
temperature for 2 h, during which time the mixture gradually
became reddish-brown. TLC indicated that only a small
amount of 1 remained. The reaction mixture was diluted with
40 mL of ether and filtered; the filtrate was washed with
aqueous NaHCO3 and then water. The organic layer was dried
over anhyd MgSO4, filtered through a thin layer of silica gel,
and concentrated in vacuo to a solid, shown by 1H NMR to
contain a small amount of 2 along with other major products.
For m ation of sp-9-[o-(â-Br om o-r,r-dim eth yleth yl)ph en -
yl]flu or en e (3). Meth od A. Rea ction of 1 w ith HBr . A
colorless solution of 1 (42.5 mg, 0.135 mmol) in chloroform (5
mL) was prepared in a 10-mL round-bottomed flask equipped
with a stir bar and septum. Stirring was begun, and HBr gas
was bubbled in, at which time the solution became yellow and
then deep red over a period of 1 h. The flask was then sealed
with a glass stopper and Parafilm, and stirring was continued
for an additional 2 h, after which time the red color faded.
The solvent was removed by rotary evaporation, leaving a pale
red solid that was filtered through silica gel with hexanes as
eluting agent. Evaporation of the filtrate left a light yellow
Meth od E. Rea ction of sp-9-(o-ter t-Bu tylp h en yl)-9-
flu or en yl Meth yl Eth er (6b) w ith HBr . Compound 6b was
prepared as reported.7b The reaction of 6b (50 mg, 0.15 mmol)
with HBr was carried out following the procedure described
above for the reaction of 1 with HBr. The observations were
essentially identical. The light yellow solid (57.3 mg) obtained
after evaporating the hexanes was shown by 1H NMR to be
composed of 3 (89.0% yield) and 4 (8.5% yield). Dry-column
chromatography with hexanes as eluting agent provided white
crystals of 3, mp 186.5-187.5 °C.
1
solid (50.8 mg) shown by H NMR to be composed of 3 (92.0%
yield) and sp-(9-o-tert-butylphenyl)fluorene (4) (7.6% yield).
Dry-column chromatography with hexanes as eluting agent
1
provided white crystalline 3, mp 186.5-187.5 °C. H NMR: δ

Halogenation of a tert-Butyl Group with HCl or HBr
J . Org. Chem., Vol. 64, No. 26, 1999 9449
Rea ction of sp-9-(o-ter t-Bu tylp h en yl)-9-flu or en ol (1)
with HI.Qu an titative For m ation of sp-9-(o-ter t-Bu tylph en -
yl)flu or en e (4). A 25-mL round-bottomed flask containing 1
(250 mg, 0.80 mmol) and CHCl3 (3 mL) and fitted with a rubber
septum was swirled to provide a colorless solution. HI gas was
bubbled in, which immediately turned the solution dark brown.
Oily brown droplets appeared at the bottom of the flask. After
the mixture was swirled occasionally over a 15-min period,
TLC (9:1 hexanes/ether) exhibited two spots, neither of which
was from 1. The reaction mixture was transferred to a
separatory funnel, the residue being washed into the funnel
with 15 mL of CHCl3, and the solution was washed sequen-
tially with aqueous Na2S2O3, aqueous NaHCO3 and water. The
now-colorless CHCl3 layer was separated, dried over anhyd
MgSO4, and rotary evaporated, leaving a pale yellow solid, 4,
(d, J ) 4.3 Hz), 137.01 (d, J ) 26.6 Hz), 140.02 (d, J ) 2.9
Hz), 148.83 (d, J ) 3.2 Hz), 149.21 (d, J ) 19.5 Hz). IR: 3048
(m), 2962(vs), 2868 (s), 1610 (w), 1490 (m), 1400 (w), 1368 (m),
1176 (s), 1012 (vs), 765 (vs), 729 (vs) cm-1. Anal. Calcd for
C23H21F: C, 87.31; H, 6.69; F, 6.00. Found: C, 87.67; H, 6.68;
F, 5.97.
Rea ction of sp-9-(o-ter t-Bu tylp h en yl)-9-flu or en ol (1)
w ith Tr iflic Acid in CDCl3. F or m a tion of 9-(o-ter t-Bu -
tylp h en yl)-9-flu or en yl Tr ifla te (Sa lt) (10) a n d NMR Id en -
t ifica t ion of 9-(o-ter t-Bu t ylp h en yl)-9-flu or en yl Ca t ion
(1a ). Triflic acid (0.02 mL, 0.23 mmol) was added to a colorless
solution of 1 (15.9 mg, 0.05 mmol) in CDCl3 (0.7 mL). The
solution turned blood red instantly. After 15 min, NMR showed
that all of 1 was consumed, sharp singlets at δ 1.51 and 0.51
appeared, and resolution of the aromatic region was poor. In
the spectra obtained after 18.5 and 49 h, the aromatic-proton
resolution was good, the intensity of the singlet at δ 0.51
increased, and the ratio of tert-butyl hydrogens (δ 1.51) to
aromatic hydrogens remained 9:12. The major component of
this deep red solution was the 9-cation 1a . The peak at δ 0.51
was believed to be from the erosion of the cap of the NMR
1
(230 mg; 97% yield) identified by H NMR and mp (179-180
°C, white crystals from hexanes-isooctane).8,12
Dyn a m ic NMR Ster eoch em ica l Stu d y of th e Rea ction
of sp-9-(o-ter t-Bu tylp h en yl)-9-flu or en ol (1) w ith HI. Initial
Formation of ap-9-(o-tert-Butylphenyl)fluorene (4a). An NMR
tube containing 1 (8.0 mg) and a trace of TMS was capped
and cooled to -50 °C in a liquid nitrogen-acetone bath. HI
was bubbled into CDCl3 to saturation, and the solution was
then cooled to -50 °C and transferred to the NMR tube. After
20 min, a 1H NMR spectrum obtained at -40 °C exhibited
sharp singlets at δ 0.69 (t-Bu) and 5.17 (H-9) associated with
the ap rotamer (4a ) of 9-(o-tert-butylphenyl)fluorene. Only a
very small singlet at δ 1.72 (t-Bu) suggested the presence of a
slight amount of the sp rotamer (4), which could have been
formed from traces of 1 stuck to the upper wall of the NMR
tube and not kept at low temperature. The ratio 4a /4 was 100:
2. No starting material was observed. An NMR spectrum
obtained when the solution warmed to -20 °C exhibited only
slightly more 4, the ratio 4a /4 being 100:5. The ratio at -10
°C was 100:14; at 0 °C, 100:36. After 25 min at room
temperature, the resonances of 4a were barely visible, the
spectrum clearly exhibiting the presence of 4 almost exclu-
sively. The conversion was quantitative.
1
tube by triflic acid. H NMR: δ 1.51 (s, 9 H), 6.88 (ddd, J )
7.8, 7.5, 0.6 Hz, 2 H), 6.96 (dd, J ) 0.6, 7.2 Hz, 4 H), 7.23 (dd,
J ) 1.5, 7.8 Hz, 1 H), 7.39 (ddd, J ) 1.2, 7.5, 7.2 Hz, 2 H), 7.48
(ddd, J ) 0.9, 7.2, 7.8, 8.1 Hz, 1 H), 7.78 (ddd, J ) 1.5, 7.5, 7.2
Hz, 1 H), 7.88 (d, J ) 8.1 Hz, 1 H). 13C NMR: δ 33.91, 38.36;
116.21, 120.41, 125.96, 126.34, 127.90, 131.34, 133.00, 136.21,
141.60, 143.48, 149.48, 149.83, 153.45, 215.66.
Rea ction of 1-OLi w ith (CH3CO)2O. P r ep a r a tion of sp-
9-(o-ter t-Bu tylp h en yl)-9-flu or en yl Aceta te (Ester ) (11).
Into a 25-mL one-necked flask equipped with a magnetic stir
bar and a septum and containing 1 (110 mg, 0.35 mmol) and
hexanes (8 mL) was bubbled argon to replace air. The mixture
was stirred, providing a colorless solution. The flask was cooled
in an ice bath, and an n-BuLi-hexanes solution (0.30 mL, 1.2
M, 0.36 mmol) was injected; the reaction mixture became light
yellow. The ice bath was removed, freshly distilled acetic
anhydride (0.15 mL, 1.59 mmol) was injected, and the mixture
was stirred for 3 h during which time white solid gradually
formed. The solid was removed by filtration, and the filtrate
was evaporated under reduced pressure to give 107 mg of a
semisolid that contained 85.6% (73.3% yield) of 11, determined
by NMR. Compound 11 was easily hydrolyzed into 1 on a TLC
plate. Recrystallization from hexanes gave white crystals of
Rea ction of sp-9-(o-ter t-Bu tylp h en yl)-9-flu or en ol (1)
w ith P yr id in e‚(HF )x. Exclu sive F or m a tion of sp-9-(o-ter t-
Bu tylp h en yl)-9-flu or oflu or en e (5). To a plastic bottle con-
taining finely powdered 1 (157 mg, 0.5 mmol) and equipped
with a stir bar was added pyridine‚(HF)x (Acros Organics; 5
mL). The reaction mixture turned red immediately. The bottle
was sealed with a rubber septum and flushed with argon, and
the mixture was stirred magnetically. The deep red color
gradually turned to light brown in 1 h. TLC (silica gel, hexanes/
ether 9:1) showed a new spot and indicated only a small
amount of 1. The mixture was extracted with hexanes (10 mL
× 3). The combined hexanes solution was evaporated in vacuo,
leaving a light brown solid, 154 mg, mp 149.5-152.5 °C (dec,
melt turned dark brown with gas evolution) shown by 1H NMR
to be composed of 5 (96%) and 1 (4%). The product is sensitive
to moisture and was hydrolyzed back to 1 on silica gel. Several
recrystallizations from hexanes provided colorless crystals, mp
154.0-155.5 °C dec. 1H NMR δ: 1.70 (d, J ) 1.5 Hz, 9 H),
6.46 (ddd, J ) 7.8, 1.8 Hz, 1 H), 6.83 (dddd, J ) 7.8, 7.2, 2.1
Hz, 1 H), 7.11 (ddd, J ) 8.1, 7.2, 1.8 Hz, 1 H), 7.21 (t, J ) 7.8
Hz, 2 H), 7.28 (m, J ) 7.5 Hz, 2 H), 7.37 (dddd, J ) 7.5, 1.5
Hz, 2 H), 7.60 (dd, J ) 8.1, 1.2, 1 H), 7.66 (d, J ) 6.9 Hz, 2 H).
13C NMR δ: 33.21 (d, J ) 12.8 Hz), 36.64, 103.95 (d, J ) 186.08
Hz), 120.17, 125.29 (d, J ) 1.8 Hz), 125.55, 127.00, 127.48,
128.73 (d, J ) 2.1 Hz), 129.82 (d, J ) 2.3 Hz), 130.46
1
11, mp 159-161.5 °C. H NMR: δ 1.82 (s, 9 H), 2.07 (s, 3 H),
6.43 (d, J ) 8.1 Hz, 1 H), 6.76 (ddd, J ) 7.2, 7.8, 0.6 Hz, 1 H);
7.04 (ddd, J ) 7.8, 1.2 Hz, 1 H); 7.19 (m, J ) 0.9, 7.5 Hz, 4 H);
7.35 (ddd, J ) 7.5, 1.8 Hz, 2 H); 7.57 (dd, J ) 8.4, 1.2 Hz, 1
H); 7.72 (d, J ) 7.5 Hz, 2 H). 13C NMR: δ 22.53, 34.04, 37.39,
91.70, 120.03, 123.72, 125.62, 126.55, 127.88, 128.43, 128.72,
131.52, 138.71, 141.09, 147.09, 150.59, 166.83. IR: 3072 (w),
1765 (vs), 1616 (w), 1372 (s), 735 (s). Anal. Calcd for
C
25H24O2: C, 84.24; H, 6.79. Found: C, 84.58; H, 6.28.
Ack n ow led gm en t. Partial support of this research
from Southern Illinois University through doctoral
fellowship (Y.H.) and Distinguished Professorship
(C.Y.M.) funding, from the Department of Chemistry
and Biochemistry Summer Undergraduate Research
Program (H.L.S.), and the University Research Founda-
tion, La J olla, is gratefully acknowledged.
J O9910280